Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria?

Abstract

Antimicrobial peptides are an abundant and diverse group of molecules that are produced by many tissues and cell types in a variety of invertebrate, plant and animal species. Their amino acid composition, amphipathicity, cationic charge and size allow them to attach to and insert into membrane bilayers to form pores by 'barrel-stave', 'carpet' or 'toroidal-pore' mechanisms. Although these models are helpful for defining mechanisms of antimicrobial peptide activity, their relevance to how peptides damage and kill microorganisms still need to be clarified. Recently, there has been speculation that transmembrane pore formation is not the only mechanism of microbial killing. In fact several observations suggest that translocated peptides can alter cytoplasmic membrane septum formation, inhibit cell-wall synthesis, inhibit nucleic-acid synthesis, inhibit protein synthesis or inhibit enzymatic activity. In this review the different models of antimicrobial-peptide-induced pore formation and cell killing are presented.

Antibacterial Hydrogels

“…They are recognized as a possible source of panacea for the treatment of antibiotic‐resistant bacterial infections 138, 139. AMPs have strong antibacterial activities against a very broad spectrum of microorganisms, including G+ and G− bacteria, fungi, and even viruses 140…”

“…138 Bai et al designed an amphiphilic peptide A 9 K 2 that could effectively inhibit both G+ and G− bacterial strains 141. The enzymatic A 9 K 2 hydrogel possessed good biocompatibility and showed excellent selectivity by favoring the adherence and spreading of mammalian cells.…”

The phospholipid code: a key component of dying cell recognition, tumor progression and host–microbe interactions

“…Importantly, CAPs often exploit an increase in negative charge on the microbial cell membrane to facilitate entry and/ or lysis. 114 Therefore, the membrane lipid composition of infectious pathogens can determine the efficacy and selectivity of CAPs, and in this way the host can target the 'pathogen phospholipid code' as a defense mechanism. For example, the membranes of many Gram-negative bacteria contain a high level of PE, compared with Gram-positive species.…”

A defensin from clam Venerupis philippinarum: Molecular characterization, localization, antibacterial activity, and mechanism of action

“…The direct antibiotic activity of AMPs is thought to be based on their cationic and amphiphilic nature, which enables these peptides to interact with negatively charged bacterial surfaces and membranes, subsequently causing membrane disruption or altering metabolic processes (Brogden, 2005;Hale and Hancock, 2007). AMPs represent potential substitutes for antibiotics due to their broad specificity against bacteria or fungi, and their anti-viral, anti-tumoral, anti-inflammatory, wound-healing, and immunomodulatory activities (Diamond et al, 2009;Otero-González et al, 2010).…”